tbuckley/cabot-search huggingface dataset:
Clinical performance of 99m sestamibi SPECT/CT imaging in differentiating oncocytic tumors from renal cell carcinoma in routine clinical practice
Authors: A. Braun, J. Schober, A. Castro Bigalli, M. Chen, K. Ginsburg, D. Magee, L. Bukavina, D.Y. Chen, A. Correa, R.E. Greenberg, M.C. Smaldone, R. Viterbo, J. Yu, R. Uzzo, A. Kutikov
Journal: European Urology (2022)
In utero origin of myelofibrosis presenting in adult monozygotic twins
Authors: Nikolaos Sousos, Máire Ní Leathlobhair, Christina Simoglou Karali, Eleni Louka, Nicola Bienz, Daniel Royston, Sally-Ann Clark, Angela Hamblin, Kieran Howard, Vikram Mathews, Biju George, Anindita Roy, Bethan Psaila, David C. Wedge, Adam J. Mead
Journal: Nature Medicine (2022)

Abstract The latency between acquisition of an initiating somatic driver mutation by a single-cell and clinical presentation with cancer is largely unknown. We describe a remarkable case of monozygotic twins presenting with CALR mutation-positive myeloproliferative neoplasms (MPNs) (aged 37 and 38 years), with a clinical phenotype of primary myelofibrosis. The CALR mutation was absent in T cells and dermal fibroblasts, confirming somatic acquisition. Whole-genome sequencing lineage tracing revealed a common clonal origin of the CALR- mutant MPN clone, which occurred in utero followed by twin-to-twin transplacental transmission and subsequent similar disease latency. Index sorting and single-colony genotyping revealed phenotypic hematopoietic stem cells (HSCs) as the likely MPN-propagating cell. Furthermore, neonatal blood spot analysis confirmed in utero origin of the JAK2V617F mutation in a patient presenting with polycythemia vera (aged 34 years). These findings provide a unique window into the prolonged evolutionary dynamics of MPNs and fitness advantage exerted by MPN-associated driver mutations in HSCs.
Results of periurethral adjustable balloons (ACT™) in the treatment of stress urinary incontinence in women after pelvic radiotherapy
Authors: F. Michel, X. Biardeau, M-A. Perrouin-Verbe, B. Peyronnet, G. Capon, X. Gamé, S. Gaillet, Q. Bandelier, G. Karsenty
Journal: European Urology (2022)
Pharmacological characterization of the β3-adrenoceptor agonists ZD7114, ZD2079 and BRL37344 in human prostate smooth muscle contraction
Authors: R. Huang, Y. Liu, A. Tamalunas, R. Waidelich, F. Strittmatter, C.G. Stief, M. Hennenberg
Journal: European Urology (2022)
RE-TUR + BCG vs. upfront BCG in high-risk non-muscle invasive bladder cancer: A feasibility phase of a randomized controlled study
Authors: F. Soria, M. Rosazza, M. Burger, E. Comperat, F. Liedberg, A. Masson-Lecomte, H. Mostafid, B.W. Van Rhijn, S.F. Shariat, M. Babjuk, R.J. Sylvester, J. Palou, P. Gontero
Journal: European Urology (2022)
OTHR-17. Guidance for providing families with autopsy research results
Authors: Ashley Meyer, Mary Beck, Andrew Cluster, Andrea Ogle, Joshua Rubin
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The Legacy Program is a project where research autopsies are performed on the brain of Neuro-Oncology patients. There continues to be growing consensus that investigators should offer their study participants results once the research project has concluded. Several organizations like the Children’s Oncology Group have established Return of Results programs however, returning research results from autopsy samples is not a common practice. Families have voiced the importance of autopsy donation and want results from that donation. To them, this donation creates a legacy for their loved one and provides hope that their contribution to research will impact the life of future patients. As researchers, this project provides a novel platform where patients and their families can directly influence new research endeavors. OBJECTIVES: We organized a retreat to disseminate research findings to the families of patients who have donated tissue. In addition to the family members, the entire research team and clinical staff were invited. Our primary aims were to evaluate participant satisfaction and obtain feedback that would be utilized for future program planning. METHODS: At the end of the retreat a de-identified, open-ended questionnaire was handed out. Six were returned and evaluated. RESULTS: All participants were in favor of the format and content that was presented and requested an invitation to future retreats. Participant feedback included how to become more involved with the Legacy Program and the request for the creation of a social media group where families could continue to connect and provide support to each other CONCLUSIONS: Our study confirmed the importance of returning autopsy results. The retreat provided needed support to the participating families. During the retreat, researchers were able to hear direct feedback from their findings and the families voiced their goals for future research. This information was invaluable and helped shape our program.
Systematic review of active surveillance for clinically localized prostate cancer to develop recommendations regarding selection, monitoring and reclassification thresholds
Authors: P-P.M. Willemse, N. Grivas, F. Zattoni, N.F. Davis, M. Lardas, P. Cornford, N. Mottet, T.B.L. Lam
Journal: European Urology (2022)
Phase 1/2 study of BLU-451, a central nervous system (CNS) penetrant, small molecule inhibitor of EGFR, in incurable advanced cancers with <i>EGFR</i> exon 20 insertion (ex20ins) mutations.
Authors: Alexander I. Spira, Helena Alexandra Yu, Lova Sun, Danny Nguyen, Paul Pearson, Jennifer Shim-Lopez, Diana Felice Hausman, Xiuning Le
Journal: Journal of Clinical Oncology (2022)

TPS9155 Background: Oncogenic EGFR ex20ins mutations, found in ̃2% of non-small cell lung cancers (NSCLC) and a small percentage of other cancers, are generally not responsive to EGFR-targeted agents that have been approved for treatment of NSCLC with a common EGFR mutation, including L858R and exon 19 deletion. Similar to these more common types of EGFR-mutated NSCLC, CNS metastases are a challenge with EGFR ex20ins NSCLC and are associated with poor outcomes. While two EGFR ex20ins-targeting drugs were recently approved by the FDA (amivantamab and mobocertinib), neither have established CNS activity. BLU-451 is a CNS penetrant, wild type-sparing, covalent small molecule inhibitor of EGFR ex20ins as well as atypical (G719C, G719S, L861Q) and common EGFR mutants. Preclinical data have shown BLU-451 to have potent antitumor activity, including in an intracranial xenograft model, which has led to its clinical development in EGFR-mutant NSCLC. Methods: BLU-451-1101 (NCT05241873) is a phase 1/2, global, open-label study designed to evaluate single-agent BLU-451 in patients with NSCLC harboring EGFR ex20ins that has progressed following prior treatment for incurable recurrent or metastatic disease. Patients with Eastern Cooperative Oncology Group performance status 0–1 and EGFR ex20ins, exon 18 G719X or exon 21 L861Q mutant NSCLC (phases 1 and 2) or other cancers except primary CNS tumors (phase 1 only) are eligible. Patients with known ROS, RAF, ALK, or EGFR C797S mutations will be excluded. Stable, asymptomatic brain metastases are permitted, and active asymptomatic brain metastases are permitted in specific cohorts. Primary endpoints are determination of maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and tolerability (phase 1), in addition to evaluation of antitumor activity at the RP2D by RECIST v1.1 (phase 2). Secondary endpoints are evaluation of pharmacokinetics (PK) and antitumor activity by RECIST v1.1.(phase 1) and PK, safety, tolerability, and CNS antitumor activity (phase 2). Dose escalation will utilize a 3+3 design with up to 6 patients per cohort in phase 1 dose escalation and up to 12 per cohort in phase 1 dose expansion. Phase 2 will enroll patients in 3 cohorts (n = 18 each): patients with prior platinum-based chemotherapy and an EGFR ex20ins-targeted agent; patients with prior platinum but no EGFR ex20ins-targeted agent; and patients with active asymptomatic brain metastases with prior platinum with or without an EGFR ex20ins-targeted agent. The study is planned for approximately 40 centers in North America, the Asia-Pacific region, and/or Europe. Clinical trial information: NCT05241873.
IMG-02. Improved prediction of postoperative paediatric cerebellar mutism syndrome using an artificial neural network
Authors: Jai Sidpra, Adam P Marcus, Ulrike Löbel, Sebastian Toescu, Derek Yecies, Gerald Grant, Kristen Yeom, David M Mirsky, Hani J Marcus, Kristian Aquilina, Kshitij Mankad
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Postoperative paediatric cerebellar mutism syndrome (pCMS) is a common but severe complication which may arise following the resection of posterior fossa tumours in children. Two previous studies have aimed to preoperatively predict pCMS, with varying results. In this work, we examine the generalisation of these models and determine if pCMS can be predicted more accurately using an artificial neural network (ANN). METHODS: An overview of reviews was performed to identify risk factors for pCMS, and a retrospective dataset collected as per these defined risk factors from children undergoing resection of primary posterior fossa tumours. The ANN was trained on this dataset and its performance evaluated in comparison to logistic regression and other predictive indices via analysis of receiver operator characteristic curves. Area under the curve (AUC) and accuracy were calculated and compared using a Wilcoxon signed rank test, with p&amp;lt;0.05 considered statistically significant. RESULTS: 204 children were included, of whom 80 developed pCMS. The performance of the ANN (AUC 0.949; accuracy 90.9%) exceeded that of logistic regression (p&amp;lt;0.05) and both external models (p&amp;lt;0.001). CONCLUSION: Using an ANN, we show improved prediction of pCMS in comparison to previous models and conventional methods.
DIPG-38. Significant tumor regression of H3K27M-mutated diffuse midline glioma of the brainstem with panobinostat: a case report.
Authors: Sonia Partap, Natasha Abadilla, Thrithi Farahzadi, Michelle Monje
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Diffuse midline glioma is a fatal CNS tumor that chiefly occurs in children. To date, standard of care has been limited to local field radiation. A histone mutation in H3K27M is seen in 80% of diffuse midline gliomas of the brainstem, also called diffuse intrinsic pontine glioma (DIPG). Panobinostat, a potent inhibitor of histone deacetylases, has shown moderate efficacy in DIPG/DMGs in preclinical models, and a dose-finding clinical trial (PBTC-047) is ongoing. We report on a case of a child with biopsy-proven H3K27M-mutated DMG of the brainstem treated off-trial with panobinostat monotherapy after radiation. METHODS: This is a case report of a 12-year-old female with H3K27M-mutated DMG of the medulla and cerebellum that exhibited gadolinium-enhancement on MRI. The patient was treated with 54 Gy focal photon radiation to the tumor field over six weeks after biopsy demonstrating the H3.3K27M mutation (H3F3A), as well as mutations in TP53, PIK3R1 and AXSL1 genes. She was not eligible for PBTC-047 due to uncontrolled hypertension. She received panobinostat as per the ongoing PBTC protocol at a dose of 28 mg/m2 given on Monday, Wednesday, and Friday on alternating weeks. She received three 28-day cycles over three months. RESULTS: The patient tolerated the therapy well, with minimal adverse reactions of low-grade abdominal pain and constipation. MRI imaging after three cycles revealed an 80% reduction in tumor volume. Together with this radiographic response, she exhibited improvement in left-sided motor strength and improved left facial sensation. Due to an unrelated need for oral surgery, panobinostat was held. MRI imaging six weeks after cessation of panobinostat revealed extensive relapse with supratentorial and spinal disease. CONCLUSION: Systemic panobinostat may demonstrate anti-tumor efficacy in some cases of H3K27M-mutated DMG. Future work is required to determine factors predictive of favorable response.
Painful Mucosal Ulcerations in a Patient With HIV
Authors: Ayan Kusari, Ursula E. Lang, Aileen Y. Chang
Journal: JAMA Dermatology (2022)

A man in his 40s with HIV presented to the emergency department with nausea, abdominal pain, bloody stools, odynophagia, and recurrent mucosal ulcers; he was found to have pancytopenia and septic shock. What is your diagnosis?
NURS-03. Effect of psychological intervention on peripherally inserted central catheterization in children with central nervous system tumors
Authors: Yangqiong Zhang, Yuliang Xiang, Fuqiang Zhang, Xing Zhang, Juan Li, Mingyao Lai, Linbo Cai
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: Peripherally inserted central catheterization (PICC) is a frequently used invasive clinical procedure in children with central nervous system (CNS) tumors. How to reduce the psychological impact brought by the operation process and increase the cooperation of children is a concern of medical staff .The study is to investigate the effect of psychological intervention with game strategy on PICC in children with CNS tumors. METHODS: A total of 120 children with CNS tumors who underwent PICC in Guangdong Sanjiu Brain Hospital from January 2019 to February 2021 were enrolled in this study. Patients were divided into two groups according to whether psychological intervention therapy was accepted during PICC, one group was the intervention group and the other group was the control group, with 60 patients in each group. Anxiety was assessed before and after PICC using the FLACC and Spence scores. T test was used to compare the scores of the two groups. RESULTS: Anxiety was found in both groups before PICC, and there was no significant statistical difference between the two groups (p &amp;gt; 0.05). The FLACC score of the two groups during PICC showed that the degree of pain in the intervention group was lower than that in the control group (P &amp;lt; 0.05). After catheterization, the anxiety score of the intervention group was significantly lower than that of the control group (P &amp;lt; 0.05). CONCLUSION: Psychological intervention based on game can reduce the medical fear of children with CNS tumors in the process of PICC and increase the cooperation of children.
The rate of venous thromboembolism in patients with non-small cell lung cancer treated with chemotherapy or check point inhibitors.
Authors: Sriharsha Singu, Veli Bakalov, Alexander M Helfand, Pragnan Kancharla, Richard White, Ahmed Khattab, Katherine Miller, Yazan Samhouri, Gene Grant Finley
Journal: Journal of Clinical Oncology (2022)

e21053 Background: Treatment with immune checkpoint inhibitors (CPI) targeting PD-1 or PD-L1 significantly improves progression free survival and overall survival in patients with non-small cell lung cancer (NSCLC). Emerging literature suggests that the proinflammatory state of CPIs may increase the risk of thromboembolism, both venous (VTE) and arterial (ATE), which is of great concern as thromboembolism remains a major cause of mortality in patients with NSCLC. We performed a retrospective cohort study to evaluate thromboembolic outcomes in patients on immunotherapy for NSCLC. Methods: We reviewed the records of all patients diagnosed with stage IV NSCLC between December 2016 and December 2019 and treated with chemotherapy, CPIs, or both in one of the largest integrated academic health systems in Western Pennsylvania. Khorana scores (to predict the risk of future VTE) were calculated for each patient based on available data at the time of diagnosis. Logistic regression analyses were done to evaluate clinical predictors of VTE. Survival outcomes were analyzed using Kaplan-Meier estimates and a log rank test was used to compare survival estimates. Data was analyzed using SPSS v26 (IBM Corp). Results: A total of 110 patients with stage IV NSCLC were identified, 87.1% had ECOG ≤2, 67.0% had adenocarcinoma and 25.7% had squamous cell carcinoma, and 39.1% had PD-L1 staining ≥50%. Immunotherapy related adverse events (IrAE) of any grade were found in 28.2%. Overall, 25.5% received chemotherapy only, 27.7% received CPIs alone, and 45.5% received chemo + CPIs. A Khorana score of ≥2 was found in 43.6% of patients. Prophylactic anticoagulation was used in 0.9% of patients. VTE was detected in 18.3% and ATE in 10.0% of the cohort; therapeutic anticoagulation was given in 14.7% of patients. Median overall survival was 25.5 months (95% CI 18.7-32.3) in patients without VTE versus 13.7 months (95% CI 3.1-24.3) in patients with a VTE diagnosis (HR 1.96, 95% CI 1.11-3.45; p = 0.02). Khorana score of ≥2 was not a significant predictor of VTE in this cohort (univariate OR 1.34, p = 0.53, multivariate OR 1.13, p = 0.81), but was associated with worse survival (HR 2.38, 95% CI 1.48-3.83, p &lt; 0.001). Conclusions: In this retrospective cohort, VTE was associated with decreased overall survival. While no significant association between elevated Khorana score and VTE was identified, elevated Khorana score at the time of diagnosis was an independent predictor of survival in patients with NSCLC. Of note, there was a low rate of prophylactic anticoagulation in this cohort.
NFB-07. Meningiomatosis in an adolescent with TRAF-7 mutation related syndrome
Authors: Marleni Torres, Nicole Jackson, Candelaria O'Farrell, Ossama Maher, Toba Niazi, John Raghed, Ziad Khatib
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Meningiomas are rare primary brain tumors in the pediatric population, associated with multiple genetic mutations. Recent description of mutations in the TRAF7gene, a pro-apoptotic E3 ubiquitin ligase, have been found in up to one quarter of non NF-2 tumors. TRAF is downregulated in human keratinocytes after inhibition of the PI3K/AKT/mTOR signaling. Germ-line mutations in this gene are associated with facial, cardiac malformations, variable intellectual deficiency, and musculoskeletal abnormalities. OBJECTIVE: We report a case of meningiomatosis in an adolescent with TRAF 7 mutation. CASE PRESENTATION: A 17 yo female with complex medical history that includes syndactyly of the left foot, small hands and digits, congenital heart disease, overgrowth of the right lower extremity with lipomatous subcutaneous tumors, connective tissue disorder variant mutation of unknown significance in the gene Col11A2, conductive hearing loss developed meningiomas of both optic nerves requiring decompression and unroofing on two separate occasions, with associated blindness. MRI brain showed bilateral optic nerve sheath enhancement, dysplasia of the corpus callosum, mild hemimegalencephaly, inter-hemispheric fissure 1.5 cm meningioma, bilateral enhancement of internal auditory canals as well as trigeminal and glossopharyngeal nerve, consistent with menigiomatosis. Pathology showed a grade I meningioma with a TRAF7 p.G536S detected by performing a 500 genomic panel (UCSF500). She was started on Everolimus and Bevacizumab. CONCLUSION: Recurrent multiple meningiomas represent a treatment challenge for neuro-oncologists. The evolving understanding of the genetics of these tumors has improved our understanding of their pathogenesis as well as treatment. TRAF 7 mutations are associated with non-NF-2 meningiomas, and distinct phenotypic features. Germ-line testing should be considered in patients with associated malformations, as targeted therapy may improve patient outcomes.
Improvement of erectile function, weight loss and reduced inflammation under long-term treatment with testosterone treatment in hypogonadal men for up to 12 years
Authors: O.M. Aboumarzouk, Y. Aksam, R.M. Al-Zoubi, M.M. Alwani, A.R. Al-Qudimat, M.A. Rejeb, A.A. Al Ansari
Journal: European Urology (2022)
A health insurance navigation intervention tool (HINT) for survivors of childhood cancer: Randomized pilot trial results from the Childhood Cancer Survivor Study.
Authors: Elyse R. Park, Anne C. Kirchhoff, Karen A. Kuhlthau, Giselle K. Perez, Aaron McDonald, Alison A. Galbraith, Tracy Ann Battaglia, Colin Ponzani, Allyson Foor, Karely Mann, Austin R. Waters, Gregory T. Armstrong, Wendy M. Leisenring, Cayley C. Bliss, Cathy Wang, Ana Lopez, Karen Donelan
Journal: Journal of Clinical Oncology (2022)

6508 Background: Childhood cancer survivors are vulnerable to being underinsured and health insurance-related financial burden. Low health insurance literacy reduces survivors’ ability to utilize health insurance. We conducted a pilot randomized controlled trial (RCT) to assess a virtually delivered health insurance navigation tool (HINT) intervention to improve health insurance literacy (HIL) and decrease financial burden. Methods: Using a multiphase, mixed methods design, we developed and tested a theoretically-driven 4-session intervention that included: 1) Learning About Survivorship Healthcare Needs, 2) Learning About Your Plan in Relation to Policy, 3) Navigating Your Plan and Obstacles, and 4) Managing Care Costs. Eligible CCSS participants were insured and had wireless device access. We assessed feasibility and preliminary efficacy of HINT versus enhanced usual care (EUC; health insurance booklet) on HIL (16-item instrument assessing knowledge and confidence with health insurance terms and activity, ACA provisions knowledge (8-items), psychological financial burden (7-items assessing worry due to medical costs), and satisfaction with health insurance coverage (1 item) using multivariable linear regression. Results: From 8/20 to 5/2021, 82 participants enrolled (39.7% participation rate); 53.7% female; 82% white, 7% Hispanic, and 7% black; 52.4% &lt;40 years of age; and 57.3% from a Medicaid expansion state. 25.6% reported previously being uninsured. 57.3% were diagnosed &lt;10 years of age, and 40.1% had ≥1 severe chronic health condition. There were gaps in health insurance literacy (HIL mean 28.5, sd=9.0; 16-60 (high-low); 39.0% were not familiar with the Affordable Care Act (ACA), and many lacked ACA provisions knowledge (e.g., appeals for coverage denials (56.1%). 82% completed 4 sessions; 92.6% completed the 5-month follow-up survey. Compared to EUC, HINT significantly improved HIL, ACA provisions knowledge, psychological financial hardship, and health insurance satisfaction (p’s ≤ 0.03). Conclusions: Findings affirm health insurance literacy gaps among a national sample of insured long-term survivors. Results support the feasibility and preliminary efficacy of HINT on improving health insurance literacy, satisfaction, and psychological financial burden. HINT is the first intervention to demonstrate improvements in long-term survivors’ health insurance literacy and psychological financial burden. Clinical trial information: NCT04520061. [Table: see text]